Carcinoma, Non Small Cell LungPhase 1NCT00934076
Tarceva and AT-101 for Patients With Advanced Non-Small Cell Lung Cancer
A Phase 1 study testing Tarceva plus AT-101 in people with Carcinoma, Non Small Cell Lung, run by University of Alabama at Birmingham.
Trial summary
The purpose of this study the safety and effectiveness of oral AT-101 when given with the standard dose of erlotinib (Tarceva)to patients who are older that 18 and who have advanced non-small cell lung cancer, who have relapsed or progressed on prior platinum-based chemotherapy. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Carcinoma, Non Small Cell Lung
- What is being tested?
- Tarceva plus AT-101
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Feb 2010to Jun 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathological proven diagnosis of NSCLC with positive EGFR status by immunohistochemistry. Patients will be considered as positive if greater than 10% of the tumor cells are positively stained by the EGFR pharmDX assay kit.
- Disease that is locally advanced, metastatic, or recurrent.
- Prior treatment with 1 or 2 chemotherapy regimens, including a platinum based regimen for advanced disease (stage IIIB with malignant pleural effusion or stage IV).
- Evidence of unidimensionally measurable disease as per Response Evaluation Criteria in Solid Tumors [RECIST].
- Radiographic evidence of disease progression during or following previous chemotherapy treatment.
- Formalin fixed, paraffin embedded tumor tissue from the initial diagnoses will be obtained.
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- Male or female, 19 years of age or older.
- ECOG performance status 0 2.
- Resolution of all acute toxic effects of prior therapy or surgical procedures (except for alopecia).
- Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of therapy. Prophylactic use of bisphosphonates in patients without bone disease, except for the treatment of osteoporosis, is not permitted.
- Ability to swallow and retain oral medication.
- Adequate organ function as defined by the following criteria:
- Hemoglobin >9.0 g/dL.
- Absolute neutrophil count (ANC) >1500/μL.
- Platelet >100,000/μL.
- Serum creatinine <1.75 × ULN.
- Serum albumin >3.0 g/dL.
- Total serum bilirubin <1.5 × ULN.
- Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) <2.5 × ULN, or AST and ALT <5 × ULN if liver function abnormalities are due to underlying malignancy
- Signed and dated informed consent indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
- Males and non-pregnant, non-lactating females age 19 years or older.
Who cannot join
- Prior treatment with >2 systemic chemotherapy based regimens for advanced disease (stages IIIB/IV).
- Prior treatment with any EGFR inhibitors (TK inhibitor or monoclonal antibody).
- Symptomatic brain metastases or spinal cord compression; subjects will be eligible after adequate treatment (radiotherapy, surgery) and having stable disease not requiring steroids.
- Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma that has been adequately treated.
- Any significant acute or chronic medical (e.g., gastrointestinal complications, myocardial infarction, unstable angina, congestive heart failure, cerebrovascular accident, infection, metabolic complications, etc.) or psychiatric conditions that would impart, in the judgment of the investigator, excess risk associated with study participation, or study drug administration.
- Known human immunodeficiency virus (HIV) infection.
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- Current treatment on other therapeutic clinical trials.
- Known hypersensitivity to gossypol, its enantiomers, or its excipients.
- Any other condition or circumstance that would, in the opinion of the Investigator, make the patient unsuitable for participation in the study.
- Patients with symptomatic hypercalcemia or hypercalcemia that is > grade 2.
- Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel are excluded. Subjects with ulcerative colitis, inflammatory bowel disease, or partial or complete small bowel obstruction are also excluded.
- Pregnancy or breastfeeding. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female patients with reproductive potential must have a negative pregnancy test within 3 days prior to enrollment. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy.
About this study
Official title: Phase I Study of Erlotinib (Tarceva) in Combination With AT-101 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
The purpose of this study the safety and effectiveness of oral AT-101 when given with the standard dose of erlotinib (Tarceva)to patients who are older that 18 and who have advanced non-small cell lung cancer, who have relapsed or progressed on prior platinum-based chemotherapy.
It is proposed that the effects of AT-101 may improve the clinical benefit of erlotinib in patients with advanced NSCLC.
Read the detailed description
Lung cancer is the leading cause of death in the United States as well as worldwide. It is estimated that approximately 215,020 new cases of lung cancer will be diagnosed in the United States in 2008, with approximately 161,840 deaths (1). The great majority of the lung cancers are grouped as non small cell lung cancer (NSCLC), and only 13% as small cell lung cancer. Most patients with NSCLC present with advanced disease (55% with stage IIIB or IV). The overall median survival of patients with advanced NSCLC treated with first line platinum based doublets is less than 12 months (8 10 months) with a 1 year and 2 year survival of 33% and 11%, respectively (2-4). Agents targeting epidermal growth factor receptor (EGFR), matrix metalloproteinase, farnesyl transferase, protein kinase C and retinoic X receptor have so far shown no survival benefit in combination with chemotherapy in advanced NSCLC (5-10).
More recently, 2 trials have shown clinical evidence of anti tumor activity with the addition of bevacizumab to first line chemotherapy in patients with advanced NSCLC (11,12). The pivotal study (EGOC 4599) responsible for the approval of bevacizumab in combination with carboplatin plus paclitaxel in selective patients with advanced non squamous cell lung cancers demonstrated a 2 month improvement in the median survival (12.3 months versus 10.3 months), and a higher objective response rate (12).
Patients with disease progression on or after first line therapy may be candidates for second line chemotherapy with either docetaxel or pemetrexed, which results in a modest improvement in survival. More recently, 2 EGFR tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, have been approved for second and third line therapy in advanced NSCLC (13,14). The effect on overall survival in genotypically uncharacterized patients was observed with erlotinib (BR21 trial), but not with gefitinib (ISEL trial), contributing to the withdrawal of gefitinib from the United States, and the approval of erlotinib as second and third line therapy in NSCLC irrespective of tumor genotype (15).
It is proposed that the effects of AT-101 on the downstream signaling pathways of the EGFR, particularly inhibition of the anti-apoptotic members Bcl-2 family of proteins, may provide an opportunity to improve the clinical benefit of erlotinib in patients with advanced NSCLC.
The safety of the combination of erlotinib with AT-101 has not been assessed. It is therefore proposed that a phase I study be performed using standard (FDA approved) dose of erlotinib (150 mg/day) with an effective dose of AT-101 (40 mg twice daily for 3 days) of a 3 week cycle.
- Conditions
- Carcinoma, Non Small Cell Lung
- Being tested
- Tarceva plus AT-101
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tarceva plus AT-101Drug
150 mg of Tarceva taken once daily in a continuous regimen expressed in 3 week cycles.
Oral AT-101 at 40 mg twice daily for 3 days of each 3 week cycle on an outpatient basis.
| Study group | Role | What they receive |
|---|---|---|
| AT-101 plus Erlotinib | Experimental | Subjects will begin study treatment at 150 mg of erlotinib taken once daily in a continuous regimen expressed in 3 week cycles.
Subjects will begin treatment with oral AT-101 at 40 mg twice daily for 3 days of each 3 week cycle on an outpatient basis. Receives: Drug: Tarceva plus AT-101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety and tolerability of erlotinib plus AT-101
Measured: Assessment of toxicity will be performed on day 15 of the first cycle, and then on day 1 of every cycle of treatment.
Secondary outcomes (1)
Evaluation of efficacy for erlotinib plus AT-101 using the binary outcome "alive without progression at 6 months (AWOP6)" as a secondary endpoint.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2009 (estimated)
- Study startFeb 2010
- Primary completionJan 2011 (estimated)
- Study completionJun 2015 (estimated)
Why it stopped: Study was never activated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non Small Cell LungStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Ascenta Therapeutics
- Investigators
- Francisco Robert, M.D., Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00934076
- Sponsor's protocol ID
- F090218006
- Other IDs
- UAB 0831
- Status last verified
- Jan 2011
- First submitted
- 6 Jul 2009
- Last updated
- 8 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Erlotinib (Tarceva) in Combination With AT-101 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT00934076
- Acronym / sponsor ID
- F090218006
- Conditions
- Carcinoma, Non Small Cell Lung
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was never activated
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Ascenta Therapeutics
- Study start
- Feb 2010
- Primary completion
- Jan 2011 (estimated)
- Study completion
- Jun 2015 (estimated)
- First posted
- 8 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study the safety and effectiveness of oral AT-101 when given with the standard dose of erlotinib (Tarceva)to patients who are older that 18 and who have advanced non-small cell lung cancer, who have relapsed or progressed on prior platinum-based chemotherapy.
It is proposed that the effects of AT-101 may improve the clinical benefit of erlotinib in patients with advanced NSCLC.
Detailed description
Lung cancer is the leading cause of death in the United States as well as worldwide. It is estimated that approximately 215,020 new cases of lung cancer will be diagnosed in the United States in 2008, with approximately 161,840 deaths (1). The great majority of the lung cancers are grouped as non small cell lung cancer (NSCLC), and only 13% as small cell lung cancer. Most patients with NSCLC present with advanced disease (55% with stage IIIB or IV). The overall median survival of patients with advanced NSCLC treated with first line platinum based doublets is less than 12 months (8 10 months) with a 1 year and 2 year survival of 33% and 11%, respectively (2-4). Agents targeting epidermal growth factor receptor (EGFR), matrix metalloproteinase, farnesyl transferase, protein kinase C and retinoic X receptor have so far shown no survival benefit in combination with chemotherapy in advanced NSCLC (5-10).
More recently, 2 trials have shown clinical evidence of anti tumor activity with the addition of bevacizumab to first line chemotherapy in patients with advanced NSCLC (11,12). The pivotal study (EGOC 4599) responsible for the approval of bevacizumab in combination with carboplatin plus paclitaxel in selective patients with advanced non squamous cell lung cancers demonstrated a 2 month improvement in the median survival (12.3 months versus 10.3 months), and a higher objective response rate (12).
Patients with disease progression on or after first line therapy may be candidates for second line chemotherapy with either docetaxel or pemetrexed, which results in a modest improvement in survival. More recently, 2 EGFR tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, have been approved for second and third line therapy in advanced NSCLC (13,14). The effect on overall survival in genotypically uncharacterized patients was observed with erlotinib (BR21 trial), but not with gefitinib (ISEL trial), contributing to the withdrawal of gefitinib from the United States, and the approval of erlotinib as second and third line therapy in NSCLC irrespective of tumor genotype (15).
It is proposed that the effects of AT-101 on the downstream signaling pathways of the EGFR, particularly inhibition of the anti-apoptotic members Bcl-2 family of proteins, may provide an opportunity to improve the clinical benefit of erlotinib in patients with advanced NSCLC.
The safety of the combination of erlotinib with AT-101 has not been assessed. It is therefore proposed that a phase I study be performed using standard (FDA approved) dose of erlotinib (150 mg/day) with an effective dose of AT-101 (40 mg twice daily for 3 days) of a 3 week cycle.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AT-101 plus Erlotinib | Experimental | Drug: Tarceva plus AT-101Subjects will begin study treatment at 150 mg of erlotinib taken once daily in a continuous regimen expressed in 3 week cycles. Subjects will begin treatment with oral AT-101 at 40 mg twice daily for 3 days of each 3 week cycle on an outpatient basis. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Pathological proven diagnosis of NSCLC with positive EGFR status by immunohistochemistry. Patients will be considered as positive if greater than 10% of the tumor cells are positively stained by the EGFR pharmDX assay kit.
- Disease that is locally advanced, metastatic, or recurrent.
- Prior treatment with 1 or 2 chemotherapy regimens, including a platinum based regimen for advanced disease (stage IIIB with malignant pleural effusion or stage IV).
- Evidence of unidimensionally measurable disease as per Response Evaluation Criteria in Solid Tumors [RECIST].
- Radiographic evidence of disease progression during or following previous chemotherapy treatment.
Key exclusion criteria (12 listed)
- Prior treatment with >2 systemic chemotherapy based regimens for advanced disease (stages IIIB/IV).
- Prior treatment with any EGFR inhibitors (TK inhibitor or monoclonal antibody).
- Symptomatic brain metastases or spinal cord compression; subjects will be eligible after adequate treatment (radiotherapy, surgery) and having stable disease not requiring steroids.
- Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma that has been adequately treated.
- Any significant acute or chronic medical (e.g., gastrointestinal complications, myocardial infarction, unstable angina, congestive heart failure, cerebrovascular accident, infection, metabolic complications, etc.) or psychiatric conditions that would impart, in the judgment of the investigator, excess risk associated with study participation, or study drug administration.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tarceva plus AT-101150 mg of Tarceva taken once daily in a continuous regimen expressed in 3 week cycles. Oral AT-101 at 40 mg twice daily for 3 days of each 3 week cycle on an outpatient basis. | Drug | AT-101 plus Erlotinib |
Primary outcome
To determine the safety and tolerability of erlotinib plus AT-101
Time frame: Assessment of toxicity will be performed on day 15 of the first cycle, and then on day 1 of every cycle of treatment.
1 secondary outcome
Evaluation of efficacy for erlotinib plus AT-101 using the binary outcome "alive without progression at 6 months (AWOP6)" as a secondary endpoint.
Time frame: 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francisco Robert, M.D. principal investigator
University of Alabama at Birmingham
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tarceva plus AT-101 in people with Carcinoma, Non Small Cell Lung, run by University of Alabama at Birmingham.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 8 May 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the safety and tolerability of erlotinib plus AT-101 (time frame: Assessment of toxicity will be performed on day 15 of the first cycle, and then on day 1 of every cycle of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2015.